A Dose-escalation Study of BIBF 1120 in Japanese Patients With Advanced Solid Tumours

A Phase I Open-label Dose-escalation Study of Continuous Twice-daily Oral Treatment With BIBF 1120 in Japanese Patients With Advanced Solid Tumours

Confirmation of BIBF 1120 administered from 150 mg twice daily (b.i.d.) to 250 mg b.i.d. as safe and tolerable treatment in Japanese patients with advanced solid tumours, overall safety, pharmacokinetic parameters, biomarkers, and efficacy of BIBF 1120.

Inclusion Criteria:

1. Male or female patients with a confirmed diagnosis of an advanced, non resectable and/or metastatic solid tumour (except for malignant lymphoma)

2. Patients who have not responded to conventional treatment, or for whom no therapy of proven efficacy was available, or who were not amenable to established forms of treatment

3. Patients recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radio-therapies (except for epilation) at least over the following periods of time:

   • four weeks after chemotherapy (at least 2 weeks after receiving antimetabolite or at least 6 weeks after nitrosourea or mitomycin C)
   • two weeks after receiving hormone therapy
   • four weeks after receiving radiation therapy (2 weeks after radiation for symptom control)
   • two weeks after receiving immunotherapy
   • four weeks after surgical procedures

4. Age 20 years or older

5. Life expectancy of at least 3 months

6. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2

7. Patients retaining a significant physiological compensatory function and without manifest marked disorders of the hematopoietic system, heart, lung, liver, kidneys, etc., i.e., patients with sufficient baseline organ function

   • An absolute neutrophil count more than 1500/mm3
   • A platelet count more than 100000/mm3
   • A haemoglobin count more than 9.0 g/dL
   • Serum creatinine less than 1.5-fold the upper limit value of the normal range
   • Bilirubin less than 1.5-fold the upper limit value of the normal range
   • Activities of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) less than 1.5-fold the upper limit value of normal range (if related to liver metastases less than 2.5-fold the upper limit value of the normal range)
   • Saturation pulse oxygen (SpO2) level not less than 90%

8. No participation in other clinical trials within 4 weeks before start of therapy within this trial

9. Written informed consent given that is consistent with ICH-GCP guidelines

Exclusion criteria

1. Brain tumour, and/or brain metastases requiring therapy
2. History of obvious pulmonary fibrosis or interstitial pneumonitis in chest X-ray including pneumoconiosis or radiation-induced pulmonary fibrosis expanding out of radiation field
3. Patients with difficulty in swallowing study medication
4. Gastrointestinal disorders that might interfere with the absorption of the study drug (Crohn's disease, ulcerative colitis, broad resection of the stomach)
5. Patients with diarrhoea greater than CTCAE grade 2
6. Patients within 4 weeks after major surgical procedures or patients with active ulcers or with injuries with incomplete wound healing
7. History of autoimmune disease
8. History of serious drug hypersensitivity
9. History of cardiac infarction or congested heart failure of New York Heart Association Classification (NYHA) II or greater within previous 6 months
10. Serious illness or concomitant non-oncological disease difficult to be controled by medication, such as active infectious disease, hepatic failure, renal failure, pulmonary fibrosis, interstitial pneumonitis, hemorrhagic tendency, heart disease (congested heart failure, angina, arrhythmia, etc.), uncontrolled, severe hypertension, and diabetes
11. Pregnancy or breastfeeding
12. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception until 4 weeks after the last trial visit
13. Patients positive in tests of hepatitis B (HBs) antigen, hepatitis C (HCV)antibody, or HIV antibody
14. Alcohol or drug abuse
15. Patient not suitable for participation in this clinical trial in the opinion of the investigator